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| {{CMG}} | | __NOTOC__ |
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| | {{CMG}} {{AE}} {{sali}} |
| {{Prostate cancer}} | | {{Prostate cancer}} |
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| ==Overview== | | ==Overview== |
| Treatment for prostate cancer may involve [[watchful waiting]], [[surgery]], [[radiation therapy]] including [[brachytherapy]] (prostate brachytherapy) and external beam radiation, [[High Intensity Focused Ultrasound (HIFU)]], [[chemotherapy]], [[cryosurgery]], hormonal therapy, or some combination. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings about potential treatments and their possible side effects. Because all treatments can have significant [[Adverse effect (medicine)|side effect]]s, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.
| | The predominant therapy for prostate cancer is [[surgical resection]]. Adjunctive [[chemotherapy]], [[radiation]], [[hormonal therapy]], [[bisphosphonates]], and [[analgesics]] may be required. |
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| ==Therapy==
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| ===Natural therapy===
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| As an alternative to active surveillance or invasive treatments, which does nothing to change the course of disease, a growing number of clinicians and researchers are looking at non-invasive ways to help men with apparently localized prostate cancer. Perhaps most convincing among this group are Dean Ornish, MD and colleagues, previously made famous for showing that aggressive lifestyle changes can reverse atherosclerosis, and now showing that PSA can be lowered in men with apparent localized prostate cancer using a vegan diet (fish allowed), regular exercise, and stress reduction.<ref>{{cite journal | last=Ornish| first=D| coauthors=Weidner G, Fair WR, et al.| title=Intensive lifestyle changes may affect the progression of prostate cancer| journal=J Urol| year=2005| volume=174| issue=3| pages=1065–70| pmid=16094059}}</ref> These results have so far proven durable after two-years' treatment.<ref>{{cite journal| last=Frattaroli| first=J| coauthors=Weidner G, Kemp C, et al.| title=Clinical events in Prostate CAncer Lifestyle Trial: Results from two years of follow-up| journal=Urology| year=2008| month=July| pmid= 18602144| volume=epub ahead of print}}</ref>
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| Many other single agents have been shown to reduce PSA, slow PSA doubling times, or have similar effects on secondary markers in men with localized cancer in short term trials, such as the Wonderful variety of pomegranate juice 8 oz daily or genistein, an isoflavone found in various legumes, 60 mg per day.<ref>{{cite journal| last=Pantuck| first=AJ| coauthors=Leppert JT, Zomorodian N, et al.| title=Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer| journal=Clin Cancer Res| year=2006| volume=12| issue=13| pages=4018–26| pmid=16818701}}</ref><ref>{{cite journal| last=Kumar| first=NB| coauthors=Cantor A, Allen K, et al.| title=The specific role of isoflavones in reducing prostate cancer risk| journal=Prostate| year=2004| volume=59| issue=2| pages=141–7| pmid= 15042614}}</ref> The potential of using multiple such agents in concert, let alone combining them with lifestyle changes, has not yet been studied but the potential is great. This is particularly true because most of these natural approaches have very low adverse effect rates, and in fact tend to help other risk factors and disease conditions such as atherosclerosis, diabetes, and risk for other cancers at the same time they are helping slow down prostate cancer. A more thorough review of natural approaches to prostate cancer has been published.<ref>{{cite journal| last=Yarnell| first=E| title=A naturopathic approach to prostate cancer. Part 2: Guidelines for treatment and prevention| journal=Altern Complemen Ther| year=1999| volume=5| issue=6| pages=360–8}}</ref>
| | ==Medical Therapy== |
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| ===Radiation therapy=== | | ===Radiation therapy=== |
| [[Image:brachytherapy.jpg|thumb|left|250px|'''[[Brachytherapy]]''' for prostate cancer is administered using "seeds," small radioactive rods implanted directly into the tumor.]][[Radiation therapy]], also known as radiotherapy, is often used to treat all stages of prostate cancer, or when surgery fails. Radiotherapy uses [[ionizing radiation]] to kill prostate cancer cells. When absorbed in tissue, [[Ionizing radiation]] such as Gamma and x-rays damage the [[DNA]] in cells, which increases the probability of apoptosis (cell death). Two different kinds of radiation therapy are used in prostate cancer treatment: [[external beam radiotherapy|external beam radiation therapy]] and [[brachytherapy]] (specifically prostate brachytherapy). | | * [[Radiotherapy]] uses [[ionizing radiation]] to kill [[prostate]] [[cancer]] cells. When absorbed in tissue, [[ionizing radiation]] such as [[Gamma]] and [[x-rays]] damage the [[DNA]] in cells, which increases the probability of [[apoptosis]]. |
| | | * Radiation therapy is commonly used in prostate cancer treatment. |
| External beam radiation therapy uses a [[linear accelerator]] to produce high-energy x-rays which are directed in a beam towards the prostate. A technique called Intensity Modulated Radiation Therapy (IMRT) may be used to adjust the radiation beam to conform with the shape of the tumor, allowing higher doses to be given to the prostate and seminal vesicles with less damage to the bladder and rectum. External beam radiation therapy is generally given over several weeks, with daily visits to a radiation therapy center. New types of radiation therapy may have fewer side effects than traditional treatment. One of these is [[Tomotherapy]].
| | * It may be used instead of [[surgery]] or after surgery in early stage prostate cancer. [[Radiation therapy]] appears to cure small [[tumors]] that are confined to the prostate just about as well as surgery.<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref> |
| | | * In advanced stages of prostate cancer, radiation is used to treat painful [[bone metastases]]. |
| [[Image:linacprostate.jpg|thumb|right|150px|[[External beam radiotherapy|External beam radiation therapy]] for prostate cancer is delivered by a linear accelerator, such as this one.]] | | * Radiation therapy is often offered to men whose medical problems make [[surgery]] more risky. |
| Permanent implant brachytherapy is a popular treatment choice for patients with low to intermediate risk features, can be performed on an outpatient basis, and is associated with good 10-year outcomes with relatively low morbidity<ref>{{cite journal| last=Nag| first=S| coauthors=Beyer D, Friedland J, Grimm P, Nath R| title=American Brachytherapy Society Recommendations for Transperineal Permanent Brachytherapy of Prostate Cancer | journal=Int. J. Rad. Onc. Biol. Phys. | year=1999| month=?| volume=44| issue=4| pages=789–799| id=?}} Review.</ref> It involves the placement of about 100 small "seeds" containing radioactive material (such as [[iodine-125]] or [[palladium-103]]) with a needle through the skin of the [[perineum]] directly into the tumor while under spinal or general anesthetic. These seeds emit [[Superficial X-ray|lower-energy X-rays]] which are only able to travel a short distance. Although the seeds eventually become inert, they remain in the prostate permanently. The risk of exposure to others from men with implanted seeds is generally accepted to be insignificant.<ref>{{cite journal| last=Perez| first=CA| coauthors=Hanks GE, Leibel SA, Zietman AL, Fuks Z, Lee WR| title=Localized carcinoma of the prostate (stages T1B, T1C, T2, and T3). Review of management with external beam radiation therapy| journal=Cancer| year=1993| month=December 1| volume=72| issue=11| pages=3156–73| pmid=7694785| doi=10.1002/1097-0142(19931201)72:11<3156::AID-CNCR2820721106>3.0.CO;2-G}} Review.</ref>
| | * Two different kinds of radiation therapy are used in prostate cancer treatment:<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref> |
| | | * Rising PSA on ADT, if testosterone level is not completely suppressed, luteinizing hormone (LH) can be measured. |
| Radiation therapy is commonly used in prostate cancer treatment. It may be used instead of surgery or after surgery in early stage prostate cancer. In advanced stages of prostate cancer radiation is used to treat painful bone metastases. Radiation treatments also can be combined with hormonal therapy for intermediate risk disease, when radiation therapy alone is less likely to cure the cancer. Some radiation oncologists combine external beam radiation and brachytherapy for intermediate to high risk situations. One study found that the combination of six months of androgen suppressive therapy combined with external beam radiation had improved survival compared to radiation alone in patients with localized prostate cancer.<ref>{{cite journal | author=D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW | title=6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial | journal=JAMA | year=2004 | pages=821–7 | volume=292 | issue=7 | pmid=15315996 | doi = 10.1001/jama.292.7.821}}</ref> Others use a "triple modality" combination of external beam radiation therapy, brachytherapy, and hormonal therapy.
| | * If its non-suppressed LH, correct administration of the GnRH analogue can be verified.<ref name="pmid26041764">{{cite journal |vauthors=Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K, Halabi S, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Drake CG, Eeles RA, Fanti S, Gleave ME, Heidenreich A, Hussain M, James ND, Lecouvet FE, Logothetis CJ, Mastris K, Nilsson S, Oh WK, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B |title=Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015 |journal=Ann Oncol |volume=26 |issue=8 |pages=1589–604 |date=August 2015 |pmid=26041764 |pmc=4511225 |doi=10.1093/annonc/mdv257 |url=}}</ref> |
| | | :* [[External beam radiotherapy|External beam radiation therapy]] |
| Radiation therapy uses high-energy rays or particles to kill cancer cells.<ref>[http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Radiation_Therapy_36.asp?rnav=cri American Cancer Society: Radiation Treatment]</ref>
| | :* [[Brachytherapy]] |
| When delivered in the correct dosage, radiation can reduce the risk of recurrence.
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| Less common applications for radiotherapy are when cancer is compressing the spinal cord, or sometimes after surgery, such as when cancer is found in the seminal vesicles, in the lymph nodes, outside the prostate capsule, or at the margins of the biopsy.
| | ====Side effects of radiation therapy==== |
| | | * Both types of [[radiation therapy]] have following adverse effects:<ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref><ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref> |
| Radiation therapy is often offered to men whose medical problems make surgery more risky. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery. However, some issues remain unresolved, such as whether radiation should be given to the rest of the pelvis, how much the [[absorbed dose]] should be, and whether hormonal therapy should be given at the same time.
| | :* [[Diarrhea]] |
| | | :* Mild [[Gastrointestinal bleeding|rectal bleeding]] |
| Side effects of radiation therapy might occur after a few weeks into treatment. Both types of radiation therapy may cause [[diarrhea]] and mild [[Gastrointestinal bleeding|rectal bleeding]] due to [[radiation proctitis]], as well as urinary incontinence and impotence. Symptoms tend to improve over time. Rates for impotence when comparing radiation to nerve-sparing surgery are similar. Radiation has lower rates of incontinence but higher rates of occasional mild rectal bleeding.<ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref> Men who have undergone external beam radiation therapy may have a slightly higher risk of later developing [[colon cancer]] and [[bladder cancer]].<ref>{{cite journal| last=Brenner| first=DJ| coauthors=Curtis RE, Hall EJ, Ron E| title=Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery| journal=Cancer| year=2000| month=January 15| volume=88| issue=2| pages=398–406| pmid=10640974| doi=10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V}}</ref> | | * [[External beam radiotherapy|External beam radiation therapy]] has following adverse effects:<ref>{{cite journal| last=Brenner| first=DJ| coauthors=Curtis RE, Hall EJ, Ron E| title=Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery| journal=Cancer| year=2000| month=January 15| volume=88| issue=2| pages=398–406| pmid=10640974| doi=10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V}}</ref> |
| | :* [[Colon cancer]] |
| | :* [[Bladder cancer]] |
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| ===Hormonal therapy=== | | ===Hormonal therapy=== |
| [[Image:prostatehormone.jpg|right|thumb|200px|'''Hormonal therapy in prostate cancer.''' Diagram shows the different organs (''purple text''), hormones (''black text and arrows''), and treatments (''red text and arrows'') important in hormonal therapy.]]
| | * [[Hormonal therapy (oncology)|Hormonal therapy]] uses medications or surgery to block prostate cancer cells from getting [[dihydrotestosterone]] ([[Dihydrotestosterone|DHT]]), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking [[Dihydrotestosterone|DHT]] often causes prostate cancer to stop growing and even shrink.<ref>{{cite journal| last=Robson| first=M|author2=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am|date=June 1996| volume=10| issue=3| pages=727–47| pmid=8773508|doi=10.1016/S0889-8588(05)70364-6}} Review.</ref> |
| [[Hormonal therapy (oncology)|Hormonal therapy]] uses medications or surgery to block prostate cancer cells from getting [[dihydrotestosterone]] (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink. However, hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate. It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.<ref>{{cite journal| last=Robson| first=M| coauthors=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am| year=1996| month=June| volume=10| issue=3| pages=727–47| pmid=8773508| doi=10.1016/S0889-8588(05)70364-6}} Review.</ref> | | * Hormonal therapy for prostate cancer targets the pathways the body uses to produce [[DHT]]. A [[feedback loop]] involving [[testicles]], [[hypothalamus]], [[pituitary]], [[adrenal]], and prostate glands to control the blood levels of [[DHT]]. First, low blood levels of [[DHT]] stimulate the [[hypothalamus]] to produce [[gonadotropin releasing hormone]] (GnRH). GnRH then stimulates the [[pituitary gland]] to produce [[luteinizing hormone]] (LH), and LH stimulates the [[testicles]] to produce testosterone. Finally, [[testosterone]] from the [[testicles]] and [[dehydroepiandrosterone]] from the [[adrenal gland]]s stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point. |
| | * Hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate.<ref>{{cite journal| last=Robson| first=M|author2=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am|date=June 1996| volume=10| issue=3| pages=727–47| pmid=8773508|doi=10.1016/S0889-8588(05)70364-6}} Review.</ref> |
| | * It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.<ref>{{cite journal| last=Robson| first=M| coauthors=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am| year=1996| month=June| volume=10| issue=3| pages=727–47| pmid=8773508| doi=10.1016/S0889-8588(05)70364-6}} Review.</ref> |
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| Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A [[feedback loop]] involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the [[hypothalamus]] to produce [[gonadotropin releasing hormone]] (GnRH). GnRH then stimulates the [[pituitary gland]] to produce [[luteinizing hormone]] (LH), and LH stimulates the [[testicles]] to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the [[adrenal gland]]s stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
| | * There are several forms of hormonal therapy:<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref><ref>{{cite journal| last=Loblaw| first=DA| coauthors=Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI; American Society of Clinical Oncology| title=American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer| journal=J Clin Oncol| year=2004| month=July 15| volume=22| issue=14| pages=2927–41| pmid=15184404| doi=10.1200/JCO.2004.04.579}} Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.</ref> |
| There are several forms of hormonal therapy:
| | :* [[Antiandrogens]] |
| | ::* [[Flutamide]] |
| | ::* [[Bicalutamide]] |
| | ::* [[Nilutamide]] |
| | ::* [[Cyproterone acetate]] |
| | :* [[Gonadotropin-releasing hormone analog|GnRH antagonists]] |
| | :* [[Estrogen ]] |
| | :* Antiadrenal therapy |
| | ::* [[Ketoconazole]] |
| | ::* [[Aminoglutethimide]] |
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| *[[Castration|Orchiectomy]] is surgery to remove the testicles. Because the testicles make most of the body's testosterone, after orchiectomy testosterone levels drop. Now the prostate not only lacks the testosterone stimulus to produce DHT, but also it does not have enough testosterone to transform into DHT. | | === Chemotherapy === |
| *[[Antiandrogens]] are medications such as [[flutamide]], [[bicalutamide]], [[nilutamide]], and [[cyproterone acetate]] which directly block the actions of testosterone and DHT within prostate cancer cells.
| | * [[Chemotherapy]] is used in the treatment of castrate resistant prostate cancer (also called hormone-refractory prostate cancer). |
| *Medications which block the production of adrenal androgens such as DHEA include [[ketoconazole]] and [[aminoglutethimide]]. Because the adrenal glands only make about 5% of the body's androgens, these medications are generally used only in combination with other methods that can block the 95% of androgens made by the testicles. These combined methods are called total androgen blockade (TAB). TAB can also be achieved using antiandrogens. | | * The most commonly used regimen combines the chemotherapeutic drug liste below: |
| *GnRH action can be interrupted in one of two ways. [[Gonadotropin-releasing hormone analog|GnRH antagonists]] suppress the production of LH directly, while [[Gonadotropin-releasing hormone analog|GnRH agonists]] suppress LH through the process of [[downregulation]] after an initial stimulation effect. [[Abarelix]] is an example of a GnRH antagonist, while the GnRH agonists include [[leuprolide]], [[goserelin]], [[triptorelin]], and [[buserelin]]. Initially, GnRH agonists ''increase'' the production of LH. However, because the constant supply of the medication does not match the body's natural production rhythm, production of both LH and GnRH decreases after a few weeks.<ref>{{cite journal| last=Loblaw| first=DA| coauthors=Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI; American Society of Clinical Oncology| title=American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer| journal=J Clin Oncol| year=2004| month=July 15| volume=22| issue=14| pages=2927–41| pmid=15184404| doi=10.1200/JCO.2004.04.579}} Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.</ref> | | :* [[Docetaxel]] |
| *A very recent Trial I study (N=21) found that [[Abiraterone|Abiraterone Acetate]] caused dramatic reduction in [[PSA]] levels and [[Tumor]] sizes in aggressive end-stage prostate cancer for 70% of patients. This is prostate cancer that resists all other treatments (e.g., castration, other hormones, etc.). Officially the impacts on life-span are not yet known because subjects have not been taking the drug very long. Larger Trial III Clinical Studies are in the works. If successful an approved treatment is hoped for around 2011.<ref>{{cite journal| last=de Bono| first=Johann| coauthors= Gerhardt Attard, Alison H.M. Reid, Timothy A. Yap, Florence Raynaud, Mitch Dowsett, Sarah Settatree, Mary Barrett, Christopher Parker, Vanessa Martins, Elizabeth Folkerd, Jeremy Clark, Colin S. Cooper, Stan B. Kaye, David Dearnaley, Gloria Lee | title= Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven| url = http://jco.ascopubs.org/cgi/content/abstract/JCO.2007.15.9749v1 | journal=J Clin Oncol| year=2004| month=July 21| volume= | issue= | pages= online| pmid=15184404| doi=10.1200/JCO.2007.15.9749| nopp=true}} Erratum in: J Clin Oncol. Early Release, published ahead of print July 21, 2008</ref><ref>{{ cite news | author = Richard Warry | title = Drug for deadly prostate cancer | url = http://news.bbc.co.uk/2/hi/health/7517414.stm | publisher = [[BBC]] | date = July 22, 2008 | accessdate = 2008-07-23 }}</ref>
| | :* [[Abiraterone]] |
| | :* [[Corticosteroid]] |
| | ::* [[Prednisone]]<ref>{{cite journal| last=Tannock| first=IF| coauthors=de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators| title=Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer| journal=N Engl J Med| year=2004| month=October 7| volume=351| issue=15| pages=1502–12| pmid=1547021| doi=10.1056/NEJMoa040720}}</ref> |
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| The most successful hormonal treatments are orchiectomy and GnRH agonists. Despite their higher cost, GnRH agonists are often chosen over orchiectomy for cosmetic and emotional reasons. Eventually, total androgen blockade may prove to be better than orchiectomy or GnRH agonists used alone.
| | ===Other Medications=== |
| | * [[Bisphosphonates]] |
| | :* [[Bisphosphonates]] such as [[zoledronic acid]] have been shown to delay [[skeletal]] [[complications]] such as [[fracture]]s or the need for [[radiation therapy]] in patients with hormone-refractory [[metastatic]] prostate cancer.<ref>{{cite journal | author=Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B | title=A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma | journal=J Natl Cancer Inst | year=2002 | pages=1458–68 | volume=94 | issue=19 | pmid=12359855}}</ref> |
| | * [[Analgesics]] |
| | :* [[Bone pain]] due to [[metastatic]] disease is treated with [[opioid]]. [[Analgesic|Pain relievers]] such as [[morphine]] and [[oxycodone]]. |
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| Each treatment has disadvantages which limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant. The loss of testosterone also causes [[Hot flush|hot flashes]], weight gain, loss of [[libido]], enlargement of the [[breast]]s ([[gynecomastia]]), impotence and [[osteoporosis]]. GnRH agonists eventually cause the same side effects as orchiectomy but may cause worse symptoms at the beginning of treatment. When GnRH agonists are first used, testosterone surges can lead to increased bone pain from metastatic cancer, so antiandrogens or abarelix are often added to blunt these side effects. Estrogens are not commonly used because they increase the risk for [[cardiovascular disease]] and [[thrombosis|blood clots]]. The antiandrogens do not generally cause impotence and usually cause less loss of bone and muscle mass. Ketoconazole can cause [[Hepatotoxicity|liver damage]] with prolonged use, and aminoglutethimide can cause skin [[rash]]es.
| | ==References== |
| | {{Reflist|2}} |
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| === Palliative care ===
| | [[Category:Disease]] |
| [[Palliative care]] for advanced stage prostate cancer focuses on extending life and relieving the symptoms of metastatic disease. As noted above [[Abiraterone|Abiraterone Acetate]] is showing some promise in treating advance stage prostate cancer. It causes a dramatic reduction in [[Prostate specific antigen|PSA]] levels and [[Tumor]] sizes in aggressive advanced-stage prostate cancer for 70% of patients. [[Chemotherapy]] may be offered to slow disease progression and postpone symptoms. The most commonly used regimen combines the chemotherapeutic drug [[docetaxel]] with a [[corticosteroid]] such as [[prednisone]].<ref>{{cite journal| last=Tannock| first=IF| coauthors=de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators| title=Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer| journal=N Engl J Med| year=2004| month=October 7| volume=351| issue=15| pages=1502–12| pmid=1547021| doi=10.1056/NEJMoa040720}}</ref> [[Bisphosphonates]] such as [[zoledronic acid]] have been shown to delay skeletal complications such as [[fracture]]s or the need for radiation therapy in patients with hormone-refractory metastatic prostate cancer.<ref>{{cite journal | author=Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B | title=A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma | journal=J Natl Cancer Inst | year=2002 | pages=1458–68 | volume=94 | issue=19 | pmid=12359855}}</ref> | | [[Category:Urology]] |
| | [[Category:Types of cancer]] |
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| [[Bone pain]] due to metastatic disease is treated with [[opioid]] [[Analgesic|pain relievers]] such as [[morphine]] and [[oxycodone]]. External beam radiation therapy directed at bone metastases may provide [[pain]] relief. Injections of certain [[radioisotope]]s, such as [[strontium-89]], [[phosphorus-32]], or [[samarium-153-ethylene diamine tetramethylene phosphonate|samarium-153]], also target bone metastases and may help relieve pain.
| | {{WH}} |
| | | {{WS}} |
| ===Androgen ablation therapy===
| | [[Category:Urology]] |
| In 1941, Charles Huggins reported that [[androgen]] ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.<ref>Huggins C, Steven RE and Hodges CV, Studies on prostatic cancer. Arch. Sug. 43:209–223, 1941.</ref> [[Androgen]] ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission an androgen-independent phenotype typically emerges, where the median overall survival is 23–37 months from the time of initiation of [[androgen]] ablation therapy.<ref>Hellerstedt BA and Pienta KJ, The current state of hormonal therapy for prostate cancer, CA Cancer J. Clin. 52: 154–179, 2002.PMID 12018929</ref> The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed.<ref>Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001 Oct;1(1):34–45. PMID 11900250</ref> Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3, and DU-145 are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express [[androgen receptor]] (AR), however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated [[transcription factor]], belongs to the steroid [[nuclear receptor]] family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. The proliferation of LNCaP cells is [[androgen]]-dependent but the proliferation of PC-3 and DU-145 cells is [[androgen]]-insensitive.Elevation of AR expression is often observed in advanced prostate [[tumor]]s in patients.<ref>Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001 May 1;61(9):3550–5. PMID 11325816</ref><ref>Ford OH 3rd, Gregory CW, Kim D, Smitherman AB, Mohler JL. Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J Urol. 2003 Nov;170(5):1817–21.PMID 14532783</ref> Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These [[androgen]]-independent LNCaP cells have elevated [[AR]] expression and express [[prostate specific antigen]] upon [[androgen]] treatment. [[Androgen]]s paradoxically inhibit the proliferation of these [[androgen]]-independent prostate [[cancer]] cells.<ref>Kokontis J, Takakura K, Hay N, Liao S. Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. Cancer Res. 1994 March 15;54(6):1566–73. PMID 7511045</ref><ref>Umekita Y, Hiipakka RA, Kokontis JM, Liao S. Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride. Proc Natl Acad Sci U S A. 1996 October 15;93(21):11802-7. PMID 8876218</ref><ref>Kokontis JM, Hsu S, Chuu CP, Dang M, Fukuchi J, Hiipakka RA, Liao S. Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity. Prostate. 2005 December 1;65(4):287-98. PMID 16015608</ref> [[Androgen]] at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived [[in vivo]] model to an [[androgen]]-stimulated phenotype in athymic mice.<ref>Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res. 2005 March 15;65(6):2082–4. PMID 15781616 </ref><ref>Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S. Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist. Cancer Res. 2006 July 1;66(13):6482–6. PMID 16818617</ref> These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients. Oral infusion of [[green tea]] [[polyphenols]], a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and [[metastasis]] as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.<ref>Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci U S A. 2001 August 28;98(18):10350-5. PMID 11504910</ref>
| | [[Category:Up-To-Date]] |
| | | [[Category:Oncology]] |
| ==References==
| | [[Category:Medicine]] |
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